Abstract
A sizeable subset of patients with the two most common organ-specific rheumatic autoimmune diseases, rheumatoid arthritis (RA) and Sjögren's syndrome (SS) develop ectopic lymphoid structures (ELS) in the synovial tissue and salivary glands, respectively. These structures are characterized by perivascular (RA) and periductal (SS) clusters of T and B lymphocytes, differentiation of high endothelial venules and networks of stromal follicular dendritic cells (FDC). Accumulated evidence from other and our group demonstrated that the formation and maintenance of ELS in these chronic inflammatory conditions is critically dependent on the ectopic expression of lymphotoxins (LT) and lymphoid chemokines CXCL13, CCL19, CCL21 and CXCL12. In this review we discuss recent advances highlighting the cellular and molecular mechanisms, which regulate the formation of ELS in RA and SS, with particular emphasis on the role of lymphoid chemokines. In particular, we shall focus on the evidence that in the inflammatory microenvironment of the RA synovium and SS salivary glands, several cell types, including resident epithelial, stromal and endothelial cells as well as different subsets of infiltrating immune cells, have been shown to be capable of producing lymphoid chemokines. Finally, we summarize accumulating data supporting the conclusion that ELS in RA and SS represent functional niches for B cells to undergo affinity maturation, clonal selection and differentiation into plasma cells autoreactive against disease-specific antigens, thus contributing to humoral autoimmunity over and above that of secondary lymphoid organs.
| Original language | English |
|---|---|
| Pages (from-to) | 62-67 |
| Number of pages | 6 |
| Journal | Immunology Letters |
| Volume | 145 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Jul 30 2012 |
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Keywords
- Activation-induced cytidine deaminase
- Autoantibodies
- Ectopic lymphoid structures
- Lymphoid chemokines
- Rheumatoid arthritis
- Sjögren's syndrome
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Role of lymphoid chemokines in the development of functional ectopic lymphoid structures in rheumatic autoimmune diseases. / Corsiero, Elisa; Bombardieri, Michele; Manzo, Antonio; Bugatti, Serena; Uguccioni, Mariagrazia; Pitzalis, Costantino.
In: Immunology Letters, Vol. 145, No. 1-2, 30.07.2012, p. 62-67.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of lymphoid chemokines in the development of functional ectopic lymphoid structures in rheumatic autoimmune diseases
AU - Corsiero, Elisa
AU - Bombardieri, Michele
AU - Manzo, Antonio
AU - Bugatti, Serena
AU - Uguccioni, Mariagrazia
AU - Pitzalis, Costantino
PY - 2012/7/30
Y1 - 2012/7/30
N2 - A sizeable subset of patients with the two most common organ-specific rheumatic autoimmune diseases, rheumatoid arthritis (RA) and Sjögren's syndrome (SS) develop ectopic lymphoid structures (ELS) in the synovial tissue and salivary glands, respectively. These structures are characterized by perivascular (RA) and periductal (SS) clusters of T and B lymphocytes, differentiation of high endothelial venules and networks of stromal follicular dendritic cells (FDC). Accumulated evidence from other and our group demonstrated that the formation and maintenance of ELS in these chronic inflammatory conditions is critically dependent on the ectopic expression of lymphotoxins (LT) and lymphoid chemokines CXCL13, CCL19, CCL21 and CXCL12. In this review we discuss recent advances highlighting the cellular and molecular mechanisms, which regulate the formation of ELS in RA and SS, with particular emphasis on the role of lymphoid chemokines. In particular, we shall focus on the evidence that in the inflammatory microenvironment of the RA synovium and SS salivary glands, several cell types, including resident epithelial, stromal and endothelial cells as well as different subsets of infiltrating immune cells, have been shown to be capable of producing lymphoid chemokines. Finally, we summarize accumulating data supporting the conclusion that ELS in RA and SS represent functional niches for B cells to undergo affinity maturation, clonal selection and differentiation into plasma cells autoreactive against disease-specific antigens, thus contributing to humoral autoimmunity over and above that of secondary lymphoid organs.
AB - A sizeable subset of patients with the two most common organ-specific rheumatic autoimmune diseases, rheumatoid arthritis (RA) and Sjögren's syndrome (SS) develop ectopic lymphoid structures (ELS) in the synovial tissue and salivary glands, respectively. These structures are characterized by perivascular (RA) and periductal (SS) clusters of T and B lymphocytes, differentiation of high endothelial venules and networks of stromal follicular dendritic cells (FDC). Accumulated evidence from other and our group demonstrated that the formation and maintenance of ELS in these chronic inflammatory conditions is critically dependent on the ectopic expression of lymphotoxins (LT) and lymphoid chemokines CXCL13, CCL19, CCL21 and CXCL12. In this review we discuss recent advances highlighting the cellular and molecular mechanisms, which regulate the formation of ELS in RA and SS, with particular emphasis on the role of lymphoid chemokines. In particular, we shall focus on the evidence that in the inflammatory microenvironment of the RA synovium and SS salivary glands, several cell types, including resident epithelial, stromal and endothelial cells as well as different subsets of infiltrating immune cells, have been shown to be capable of producing lymphoid chemokines. Finally, we summarize accumulating data supporting the conclusion that ELS in RA and SS represent functional niches for B cells to undergo affinity maturation, clonal selection and differentiation into plasma cells autoreactive against disease-specific antigens, thus contributing to humoral autoimmunity over and above that of secondary lymphoid organs.
KW - Activation-induced cytidine deaminase
KW - Autoantibodies
KW - Ectopic lymphoid structures
KW - Lymphoid chemokines
KW - Rheumatoid arthritis
KW - Sjögren's syndrome
UR - http://www.scopus.com/inward/record.url?scp=84862186837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862186837&partnerID=8YFLogxK
U2 - 10.1016/j.imlet.2012.04.013
DO - 10.1016/j.imlet.2012.04.013
M3 - Article
VL - 145
SP - 62
EP - 67
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
IS - 1-2
ER -